Close physical linkage of human troponin genes: Organization, sequence, and expression of the locus encoding cardiac troponin I acid slow skeletal troponin T

Based on chromosomal mapping data, we recently revealed an unexpected linka ge of troponin genes in the human genome: the six genes encoding striated m uscle troponin I and troponin T isoforms are located at three chromosomal s ites, each of which carries a troponin I-troponin T gene pair. Here we have investigated the organization of these genes at the DNA level in isolated P1 and PAC genomic clones and demonstrate close physical linkage in two cas es through the isolation of individual clones containing a complete troponi n I-troponin T gene pair. As an initial step toward fully characterizing th is pattern of linkage, we have determined the organization and complete seq uence of the locus encoding cardiac troponin I and slow skeletal troponin T and thereby also provide the first determination of the structure and sequ ence of a slow skeletal troponin T gene. Our data show that the genes are o rganized head to tail and are separated by only 2.6 kb of intervening seque nce. In contrast to other troponin genes, and despite their close proximity , the cardiac troponin I and slow skeletal troponin T genes show independen t tissue-specific expression. Such close physical linkage has implications for the evolution of the troponin gene families, for their regulation, and for the analysis of mutations implicated in cardiomyopathy. (C) 1999 Academ ic Press.